Journal of Bioequivalence & Bioavailability

Abstract

Design In Vitro and in Vivo Characterization of Chitosan-Dextran Sulfate Microparticles for Oral Delivery of Insulin

Mikhail A. Pechenkin, Nadezhda G. Balabushevich, Ivan N. Zorov, Lubov K. Staroseltseva, Elena V. Mikhalchik, Vladimir A. Izumrudov and Natalia I. Larionova

Microparticles were fabricated by layer-by-layer deposition of chitosan (Ch) and dextran sulfate (DS) on microag - gregates formed by human insulin and DS. Consecutive treatment of the negatively charged microaggregates with Ch, DS, and Ch yielded small (ca. 10 μm) positively charged microparticles with high insulin encapsulation efficiency (65% of initial amount of insulin) and loading (50% w/w). Virtually all immobilized protein remained insoluble in the pH range 1.0–6.0 corresponding to the aggressive media of stomach and upper small intestine, while at pH 7.4, about 90% of the insulin was released during one-hour incubation. Encapsulated insulin was more resistant to the protease action than native insulin in solution: after 1-h incubation in simulated pancreatic juice only 60% of encap - sulated insulin degraded, while insulin in solution degraded almost completely. Experiments in vivo demonstrated that insulin encapsulated in microparticles preserved biological activity and exerted a prolonged hypoglycemic effect after peroral administration in rabbits and diabetic rats. Bioavailability of the encapsulated insulin administered per os was 11%. The produced microparticles are biocompatible, biodegradable, and mucoadhesive and may be used for the development of oral insulin delivery systems in humans.